Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy
Standard
Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy. / Klusa, Daria; Lohaus, Fabian; Franken, Andre; Baumbach, Marian; Cojoc, Monica; Dowling, Paul; Linge, Annett; Offermann, Anne; Löck, Steffen; Hušman, Dejan; Rivandi, Mahdi; Polzer, Bernhard; Freytag, Vera; Lange, Tobias; Neubauer, Hans; Kücken, Michael; Perner, Sven; Hölscher, Tobias; Dubrovska, Anna; Krause, Mechthild; Kurth, Ina; Baumann, Michael; Peitzsch, Claudia.
In: INT J CANCER, Vol. 152, No. 12, 15.06.2023, p. 2639-2654.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy
AU - Klusa, Daria
AU - Lohaus, Fabian
AU - Franken, Andre
AU - Baumbach, Marian
AU - Cojoc, Monica
AU - Dowling, Paul
AU - Linge, Annett
AU - Offermann, Anne
AU - Löck, Steffen
AU - Hušman, Dejan
AU - Rivandi, Mahdi
AU - Polzer, Bernhard
AU - Freytag, Vera
AU - Lange, Tobias
AU - Neubauer, Hans
AU - Kücken, Michael
AU - Perner, Sven
AU - Hölscher, Tobias
AU - Dubrovska, Anna
AU - Krause, Mechthild
AU - Kurth, Ina
AU - Baumann, Michael
AU - Peitzsch, Claudia
N1 - This article is protected by copyright. All rights reserved.
PY - 2023/6/15
Y1 - 2023/6/15
N2 - Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression. We hypothesize that markers indicative of radioresistance, stemness and/or bone tropism may have a prognostic potential to identify patients profiting from metastases-directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n = 24) during radiotherapy with CellSearch, multicolor flow cytometry and imaging cytometry. Analysis of copy-number alteration indicates a polyclonal CTC population that changes after radiotherapy. CTCs were found in 8 out of 24 patients (33.3%) and were associated with a shorter time to biochemical progression after radiotherapy. Whereas the total CTC count dropped after radiotherapy, a chemokine receptor CXCR4-expressing subpopulation representing 28.6% of the total CTC population remained stable up to 3 months. At once, we observed higher chemokine CCL2 plasma concentrations and proinflammatory monocytes. Additional functional analyses demonstrated key roles of CXCR4 and CCL2 for cellular radiosensitivity, tumorigenicity and stem-like potential in vitro and in vivo. Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK+ CXCR4+ CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis-directed radiotherapy.
AB - Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression. We hypothesize that markers indicative of radioresistance, stemness and/or bone tropism may have a prognostic potential to identify patients profiting from metastases-directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n = 24) during radiotherapy with CellSearch, multicolor flow cytometry and imaging cytometry. Analysis of copy-number alteration indicates a polyclonal CTC population that changes after radiotherapy. CTCs were found in 8 out of 24 patients (33.3%) and were associated with a shorter time to biochemical progression after radiotherapy. Whereas the total CTC count dropped after radiotherapy, a chemokine receptor CXCR4-expressing subpopulation representing 28.6% of the total CTC population remained stable up to 3 months. At once, we observed higher chemokine CCL2 plasma concentrations and proinflammatory monocytes. Additional functional analyses demonstrated key roles of CXCR4 and CCL2 for cellular radiosensitivity, tumorigenicity and stem-like potential in vitro and in vivo. Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK+ CXCR4+ CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis-directed radiotherapy.
U2 - 10.1002/ijc.34457
DO - 10.1002/ijc.34457
M3 - SCORING: Journal article
C2 - 36733230
VL - 152
SP - 2639
EP - 2654
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 12
ER -